How Infection and Inflammation Can Lead to Cancer

WASHINGTON, D.C. — New research is emerging that suggests a link between infection-related diseases and risk of cancer, according to findings presented here at the American Association for Cancer Research 101st Annual Meeting 2010.

“Chronic or recurrent inflammatory conditions appear to contribute to the development of a diverse array of cancers, and tackling these conditions early could be an avenue for prevention,” said William G. Nelson V, M.D., Ph.D., professor and director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

Nelson will host a press conference on infection, inflammation and cancer at the Annual Meeting in room 142 of the Walter E. Washington Convention Center on Monday, April 19, at 1 p.m. ET.

Reporters who cannot attend in person can call in using the following information:

According to Nelson, the emerging data on the relationship between infections and cancer suggest a need for synergy between the cancer and infectious disease research communities.

“How we alter the bacteria levels in our body is a complex issue, but there is a potential to develop cancer prevention strategies,” said Nelson.

The following abstracts will be presented at the press conference:

5353. Identification of a subset of AIDS-related lymphoma (ARL) containing HIV-infected macrophages that is immunophenotypically distinct from EBV positive ARL

Researchers at the University of California, San Francisco, have identified HIV-infected macrophages that are associated with more than half of AIDS-related lymphoma (ARL) in the post-highly active antiretroviral therapy (HAART) era.

“The frequency of this type of tumor is double that from the pre-HAART era and it is present in all subtypes of lymphoma,” said Leanne C. Huysentruyt, Ph.D., assistant research scientist at the University of California, San Francisco.

The risk of developing non-Hodgkin lymphoma is 60 times greater in patients with HIV, despite the initiation of HAART — an aggressive treatment regimen of at least three anti-retroviral drugs that attack different parts of HIV to suppress viral replication.

Using specimen data from the AIDS and Cancer Specimen Resource (from 1982 to 2007), Huysentruyt and colleagues investigated the incidence of HIV-infected lymphomas in the pre- and post-HAART eras to determine if HIV-positive lymphomas have a specific immunophenotype.

In the current study, the researchers evaluated tissue microarrays containing more than 150 ARLs for the presence of HIV.

“In the case of cells already infected, such as macrophage viral reservoirs, HAART has little or no effect. This suggests that HIV-infected macrophages in ARLs must be relatively long-lived and unaffected by anti-retroviral therapy,” she said. “Therefore, targeting HIV-infected macrophages for drug development may be an effective adjunct to current anti-lymphoma therapies.”

The frequency of the Epstein-Barr virus, another cancer-causing virus of the herpes family that was previously associated with ARL, did not change after the introduction of HAART.

Patients with AIDS are 100 times more likely to get non-Hodgkin lymphoma than the general population, and researchers have uncovered new information that suggests circulating cytokine levels may be playing a role in this increased risk.

“Although medicines that fight AIDS are becoming more effective, cancer remains a real risk among these patients. We need to keep working toward understanding the mechanisms that predispose people to certain cancers,” said Charles S. Rabkin, M.D., senior investigator at the National Cancer Institute.

Cancer was one of the first clues that led researchers to identify AIDS in the early 1980s. Since then, researchers have been working to discover why patients with AIDS are at greater risk of cancer than the general population.

For the current study, Rabkin and colleagues used prospective cohort studies to examine prediagnostic blood samples from 66 patients with AIDS and non-Hodgkin lymphoma and 186 lymphoma-free controls. These patient groups had similar ages, racial composition and gender.

The researchers measured 30 separate cytokines and found that nine of them had significantly higher levels in patients who subsequently developed lymphoma.

Researchers also examined the link between Epstein-Barr virus (EBV), a cancer-causing virus of the herpes family, and non-Hodgkin lymphoma but found no association.

“If these findings are confirmed, the next step would be to try to determine if we can modify cytokine levels in some way to make lymphoma prevention more effective in this population,” said Rabkin.

The bacterium Helicobacter pylori (H. pylori) increases the risk of colorectal polyps in blacks and may also increase their risk of colon cancer.

Presence of H. pylori is often asymptomatic, but Duane T. Smoot, M.D., chief of the gastrointestinal division at Howard University, Washington, D.C., suggested that there is more at stake than bacterial related illnesses.

“Not everyone gets sick from H. pylori infection and there is a legitimate concern about overusing antibiotics to treat it,” said Smoot. “However, the majority of the time these polyps will become cancerous if not removed, so we need to screen for the bacteria and treat it as a possible cancer prevention strategy.”

The link between H. pylori and cancer has been suggested before for other organ sites and ethnic groups, but the findings have been a subject of debate.

Smoot and colleagues observed 1,262 black participants who underwent bidirectional gastrointestinal endoscopy on the day they were enrolled. They assessed H. pylori status using immunohistochemistry on gastric specimens.

Results showed that colorectal polyps were 50 percent more prevalent in patients infected with H. pylori (43 percent) than in patients who did not have H. pylori (34 percent). Furthermore, there was a trend toward larger polyp size in infected patients. H. pylori status did not affect the histopathology or location of the polyps.

2791. Blood C-reactive protein levels and colon cancer risk

Circulating C-reactive protein (CRP), a marker of low-grade systemic inflammation, is associated with an increased risk of colon cancer.

“Elevated CRP levels may be considered as a risk marker, but not necessarily a cause, for the carcinogenic process of colon cancer,” said Gong Yang, M.D., M.P.H., research associate professor at Vanderbilt University, Nashville, Tenn.

CRP is a protein found in the blood; levels rise in response to inflammation throughout the body. Yang and colleagues at the Vanderbilt-Ingram Cancer Center evaluated the link between CRP levels and colon cancer risk, and the potential effect of time on CRP measures.

Using the Shanghai Women’s Health Study, the researchers conducted a case-control study of 338 cases of colorectal cancer and 451 individually matched controls with up to 10 years of follow-up.

CRP levels were positively associated with colon cancer risk in an analysis of 209 cases of colon cancer and 279 controls, according to Yang. Women in the highest quartile of CRP had a 2.5-fold increased risk of colon cancer compared to those in the lowest quartile. This risk was, however, much greater for women with higher levels of CRP measured in blood samples collected close in time to disease diagnosis.

“The positive association between circulating CRP and colon cancer observed in this and some previous studies may be partly explained by cancer-induced inflammation,” Yang said.

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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, the AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 31,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowship and career development awards. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. The AACR publishes six major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.